#METABOLOMICS WORKBENCH hjpainter_20210117_124420_mwtab.txt DATATRACK_ID:2400 STUDY_ID:ST001652 ANALYSIS_ID:AN002699 PROJECT_ID:PR001058
VERSION             	1
CREATED_ON             	January 19, 2021, 3:46 pm
#PROJECT
PR:PROJECT_TITLE                 	Atypical Molecular Basis for Drug Resistance to Mitochondrial Function
PR:PROJECT_TITLE                 	Inhibitors in AQ: A Plasmodium falciparum
PR:PROJECT_SUMMARY               	In this study, we present a clear genotype for the P. falciparum SB1-A6
PR:PROJECT_SUMMARY               	acridone-resistant clonal parasite strain and, through a combination of targeted
PR:PROJECT_SUMMARY               	and whole-cell methods, establish that the mechanism of resistance to both
PR:PROJECT_SUMMARY               	cytochrome bc1 and DHODH inhibitors results from the contribution of multiple
PR:PROJECT_SUMMARY               	genetic polymorphisms. We find that P. falciparum SB1-A6 accumulates both a copy
PR:PROJECT_SUMMARY               	number variation and a specific mutation in PfDHODH, and both of these genetic
PR:PROJECT_SUMMARY               	polymorphisms contribute to the panresistant phenotype. This study uncovers a
PR:PROJECT_SUMMARY               	mechanism of cross-resistance between PfDHODH and mtETC inhibitors and serves as
PR:PROJECT_SUMMARY               	a cautionary note to future antimalarial combination therapy formulations
PR:PROJECT_SUMMARY               	containing such drugs.
PR:INSTITUTE                     	U.S. Food & Drug Administration
PR:LAST_NAME                     	Painter
PR:FIRST_NAME                    	Heather
PR:ADDRESS                       	10903 New Hampshire Ave., WO 52/72-5324, Silver Spring, MD 20993
PR:EMAIL                         	Heather.Painter@fda.hhs.gov
PR:PHONE                         	240-402-2040
#STUDY
ST:STUDY_TITLE                   	Atypical Molecular Basis for Drug Resistance to Mitochondrial AQ: A Function
ST:STUDY_TITLE                   	Inhibitors in Plasmodium falciparum
ST:STUDY_SUMMARY                 	In this study, we present a clear genotype for the P. falciparum SB1-A6
ST:STUDY_SUMMARY                 	acridone-resistant clonal parasite strain and, through a combination of targeted
ST:STUDY_SUMMARY                 	and whole-cell methods, establish that the mechanism of resistance to both
ST:STUDY_SUMMARY                 	cytochrome bc1 and DHODH inhibitors results from the contribution of multiple
ST:STUDY_SUMMARY                 	genetic polymorphisms. We find that P. falciparum SB1-A6 accumulates both a copy
ST:STUDY_SUMMARY                 	number variation and a specific mutation in PfDHODH, and both of these genetic
ST:STUDY_SUMMARY                 	polymorphisms contribute to the panresistant phenotype. This study uncovers a
ST:STUDY_SUMMARY                 	mechanism of cross-resistance between PfDHODH and mtETC inhibitors and serves as
ST:STUDY_SUMMARY                 	a cautionary note to future antimalarial combination therapy formulations
ST:STUDY_SUMMARY                 	containing such drugs.
ST:INSTITUTE                     	U.S. Food & Drug Administration
ST:LAST_NAME                     	Painter
ST:FIRST_NAME                    	Heather
ST:ADDRESS                       	10903 New Hampshire Ave., WO 52/72-5324, Silver Spring, MD 20993
ST:EMAIL                         	Heather.Painter@fda.hhs.gov
ST:PHONE                         	240-402-2040
ST:PUBLICATIONS                  	DOI:10.1128/AAC.02143-20
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Plasmodium falciparum
SU:TAXONOMY_ID                   	5833
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	10_D6_CT1	10_D6_CT1	Genotype:Wild-type | Treatment:Control	RAW_FILE_NAME=10_D6_CT1.mzxml
SUBJECT_SAMPLE_FACTORS           	18_D6_CT2	18_D6_CT2	Genotype:Wild-type | Treatment:Control	RAW_FILE_NAME=18_D6_CT2.mzxml
SUBJECT_SAMPLE_FACTORS           	29_D6_CT3	29_D6_CT3	Genotype:Wild-type | Treatment:Control	RAW_FILE_NAME=29_D6_CT3.mzxml
SUBJECT_SAMPLE_FACTORS           	12_D6_AT1	12_D6_AT1	Genotype:Wild-type | Treatment:Atovaquone	RAW_FILE_NAME=12_D6_AT1.mzxml
SUBJECT_SAMPLE_FACTORS           	16_D6_AT2	16_D6_AT2	Genotype:Wild-type | Treatment:Atovaquone	RAW_FILE_NAME=16_D6_AT2.mzxml
SUBJECT_SAMPLE_FACTORS           	25_D6_AT3	25_D6_AT3	Genotype:Wild-type | Treatment:Atovaquone	RAW_FILE_NAME=25_D6_AT3.mzxml
SUBJECT_SAMPLE_FACTORS           	11_D6_DT1	11_D6_DT1	Genotype:Wild-type | Treatment:DSM-1	RAW_FILE_NAME=11_D6_DT1.mzxml
SUBJECT_SAMPLE_FACTORS           	17_D6_DT2	17_D6_DT2	Genotype:Drug Resistant | Treatment:DSM-1	RAW_FILE_NAME=17_D6_DT2.mzxml
SUBJECT_SAMPLE_FACTORS           	7_A6_CT1	7_A6_CT1	Genotype:Drug Resistant | Treatment:Control	RAW_FILE_NAME=7_A6_CT1.mzxml
SUBJECT_SAMPLE_FACTORS           	21_A6_CT2	21_A6_CT2	Genotype:Drug Resistant | Treatment:Control	RAW_FILE_NAME=21_A6_CT2.mzxml
SUBJECT_SAMPLE_FACTORS           	31_A6_CT3	31_A6_CT3	Genotype:Drug Resistant | Treatment:Control	RAW_FILE_NAME=31_A6_CT3.mzxml
SUBJECT_SAMPLE_FACTORS           	9_A6_AT1	9_A6_AT1	Genotype:Drug Resistant | Treatment:Atovaquone	RAW_FILE_NAME=9_A6_AT1.mzxml
SUBJECT_SAMPLE_FACTORS           	19_A6_AT2	19_A6_AT2	Genotype:Drug Resistant | Treatment:Atovaquone	RAW_FILE_NAME=19_A6_AT2.mzxml
SUBJECT_SAMPLE_FACTORS           	28_A6_AT3	28_A6_AT3	Genotype:Drug Resistant | Treatment:Atovaquone	RAW_FILE_NAME=28_A6_AT3.mzxml
SUBJECT_SAMPLE_FACTORS           	8_A6_DT1	8_A6_DT1	Genotype:Drug Resistant | Treatment:DSM-1	RAW_FILE_NAME=8_A6_DT1.mzxml
SUBJECT_SAMPLE_FACTORS           	20_A6_DT2	20_A6_DT2	Genotype:Drug Resistant | Treatment:DSM-1	RAW_FILE_NAME=20_A6_DT2.mzxml
SUBJECT_SAMPLE_FACTORS           	26_A6_DT3	26_A6_DT3	Genotype:Drug Resistant | Treatment:DSM-1	RAW_FILE_NAME=26_A6_DT3.mzxml
#COLLECTION
CO:COLLECTION_SUMMARY            	Cells were pelleted and the media aspirated prior to methanol extraction
CO:SAMPLE_TYPE                   	Plasmodium cells
#TREATMENT
TR:TREATMENT_SUMMARY             	Trophozoite-stage Plasmodium infected RBCs were treated with 10x IC50 of either
TR:TREATMENT_SUMMARY             	drug for 2.5 hours
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	90% Methanol/10% water at 50:1 solvent/cell pellet followed by vortexing and
SP:SAMPLEPREP_SUMMARY            	clarification via centrifugation
SP:PROCESSING_METHOD             	Lysis
SP:PROCESSING_STORAGE_CONDITIONS 	4℃
SP:EXTRACT_CLEANUP               	Clarification via centrifugation followed by nitrogen drying
SP:EXTRACT_STORAGE               	-80℃
SP:SAMPLE_RESUSPENSION           	6X pellet volume of HPLC H2O
SP:SAMPLE_SPIKING                	Internal Standard 13C4, 15N1-Aspartate used for sample preparation normalizer
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Low pH polar
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Exactive Orbitrap Plus
CH:COLUMN_NAME                   	Phenomenex Synergi Hydro RP (100 x 2mm, 2.5um)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	Proprietary analytical software for integration and peak picking
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	intensity
MS_METABOLITE_DATA_START
Samples	8_A6_DT1	9_A6_AT1	10_D6_CT1	11_D6_DT1	12_D6_AT1	16_D6_AT2	17_D6_DT2	7_A6_CT1	19_A6_AT2	20_A6_DT2	21_A6_CT2	25_D6_AT3	26_A6_DT3	28_A6_AT3	29_D6_CT3	31_A6_CT3	18_D6_CT2
Factors	Genotype:Drug Resistant | Treatment:DSM-1	Genotype:Drug Resistant | Treatment:Atovaquone	Genotype:Wild-type | Treatment:Control	Genotype:Wild-type | Treatment:DSM-1	Genotype:Wild-type | Treatment:Atovaquone	Genotype:Wild-type | Treatment:Atovaquone	Genotype:Drug Resistant | Treatment:DSM-1	Genotype:Drug Resistant | Treatment:Control	Genotype:Drug Resistant | Treatment:Atovaquone	Genotype:Drug Resistant | Treatment:DSM-1	Genotype:Drug Resistant | Treatment:Control	Genotype:Wild-type | Treatment:Atovaquone	Genotype:Drug Resistant | Treatment:DSM-1	Genotype:Drug Resistant | Treatment:Atovaquone	Genotype:Wild-type | Treatment:Control	Genotype:Drug Resistant | Treatment:Control	Genotype:Wild-type | Treatment:Control
guanosine	23491.39	36535.75	13252.27	20738.21	24212.38	28929.9	37339.56	15769.59	28281.99	26704.11	17323.06	31144.74	22244.17	29377.78	12914.62	25773.99	14796.32
dCMP	73029.23	104001.3	42961.21	71134.24	101599.7	69906.87	116546.4	63552.24	96952.6	60679.34	66237.61	119144.3	84174.02	94060.24	43244.79	84952.91	53755
N-acetyl-glucosamine-1/6-phosphate	12851.59	123735.1	10528.24	12051.92	11623.75	11479.34	16590.08	9885.634	21235.51	12360.83	12632	15959.18	15484.93	14112.2	8968.976	11185.37	9912.374
7-methylguanosine	29998.17	24728.52	26196.97	24344.65	25422.59	27763.7	43918.54	25375.36	28681.22	31258.31	30770.01	34110.96	28501.35	32067.59	23250.74	26957.15	31897.61
S-methyl-5'-thioadenosine	29719.91	21559.47	31480.76	31949.92	18455.3	20946.42	40753.55	27148.42	22796.93	34379.62	30707.1	32066.4	26360.03	24772.1	27463.94	30587.6	32059.15
D-sedoheptulose-1/7-phosphate	29469.71	53453.03	13995.12	17366.69	49963.41	59332.98	34397.56	16137.37	50013.96	24931.24	25034.22	71935.73	16652.18	54399.89	8179.094	17387.97	14585.2
glutathione	4139122	3378104	5191392	4856440	4412926	3337105	6616798	3476081	5208263	5684200	2733085	6159718	6586544	4504093	4760092	4276558	5592332
6-phospho-D-gluconate	1088808.051	1582309.84	1026440.567	1122583.58	1480351.03	1494124.024	1400644.517	1093341.276	1804753.79	1067751.659	1109614.8	1832924.221	1183457.327	1639988.45	948919.174	1159121.274	1111201.255
inosine	30150.25	38875.44	19928.69	32692.26	35483.89	36986.26	49473.04	26359.55	34254.37	41969.57	30186.77	50328.28	24961.58	45447.01	19393.79	46405.54	24099.22
1_3-diphopshateglycerate	290746.6	166285.6	922587.6	6103.357	258752.8	1294433	241763	2103498	100931.5	1702384	5989.189	1311254	64475.76	210077.8	460682.6	6960.776	40040.02
2_3-Diphosphoglyceric acid	289575.8	165768	921893.3	6103.357	258752.8	1293107	240794.6	2100134	27248.04	1700185	5989.189	1308925	63605.38	210077.8	460104.5	6960.776	39528.25
dTMP	785637.1	1029503	406266.8	701300.3	1098640	1058235	1160690	633149.3	944689.1	721791	632783.8	1351319	722963.9	1008619	303512.7	722643.2	493927.8
CMP	813004.2	961376.9	571234.9	762075.1	859903.6	770823.5	1028706	727063.9	964942.3	749073.3	767709.2	990111.7	885137	882002.8	568981.8	835826.8	651915.4
UMP	2877373	3371489	2156647	3048125	3198268	2822838	3694547	2727259	3220307	2735383	2824881	3609555	3058620	3284131	2235890	3167137	2461462
cyclic-AMP	62071.3	44922.56	51044.32	55503.65	41391.42	45803.07	70922.87	54734.59	58152.44	57149.75	58276.51	47682.81	53492.29	54284.15	49387.63	60617.83	55581.16
dAMP	236822.28	334252.603	133476.765	219132.29	356096.624	309703.505	358298.04	184515.962	282770.762	225022.509	177847.336	420070.229	216646.005	276106.162	92110.873	218963.072	148683.468
aminoimidazole carboxamide ribonucleotide	1212.744	2458.755	226.521	1164.257	750.6739	1197.057	1629.584	1122.7	6051.928	801.6559	1583.884	727.4086	1504.609	1683.003	366.3175	1179.016	664.9979
fructose-1-6-bisphosphate	288181.32	501154.28	226114.01	320393.35	336100.99	288148.14	253890.24	296090.95	977807	221078.09	435096.87	209304.98	222983.33	345737.47	338492.5	321536.7	248359.81
dGMP	5221378	5158214	4417368	5099991	5028930	5113092	6283122	4753390	5301880	4993431	4519026	5982560	4980336	5422864	3652901	5066288	4405048
D-erythrose-4-phosphate	6550.531	8470.152	4591.4798	6816.279	8811.861	7857.043	7962.992	6796.827	15731.892	6242.172	9249.852	9499.99	7400.22	9277.583	9145.364	6519.901	5581.719
NG-dimethyl-L-arginine	7492.919	6128.083	6954.446	5640.798	7593.692	7638.871	7619.42	7645.794	6953.402	6395.485	7892.189	9147.219	7741.954	11078.76	4891.588	9064.587	7313.4
tryptophan	29057.21	58044.88	21371.01	34646.99	48580.47	34849.99	25333.36	30536.51	127474.8	19909.18	55224.14	25109.58	24492.21	36248.44	41420.79	37006.64	23596.77
pantothenate	19444.34	54314.65	11510.96	19622.22	27951.25	22223.66	16777.28	18270.87	129940	9361.231	31289.19	17309.57	12869.81	29195.52	11986	17246.26	11842.97
AMP	5221378	5158214	4417368	5099991	5028930	5113092	6283122	4753390	5301880	4993431	4519026	5982560	4980336	5422864	3652901	5066288	4405048
thymidine	3101.935	6623.547	2032.119	3402.785	7576.864	6980.651	7416.224	1387.687	5472.909	3773.874	3457.93	8542.21	4685.497	5945.143	1748.894	3048.601	2505.991
glucose-6-phosphate	1867740	1685409	1834437	1885878	1707141	1979756	2203738	1785624	1813998	1829814	1815990	2257618	1937291	1935254	1800785	1916929	1723025
glucose-1-phosphate	1867740	1685409	1834437	1885878	1707141	1979756	2203738	1785624	1813998	1829814	1815990	2257618	1937291	1935254	1800785	1916929	1723025
dTTP	13150.64	19645.8	16680.36	11885.75	16497.18	24901.83	12313.23	14167.87	26309.78	33791.11	8664.253	23073.41	12938.53	18374.09	18428.4	3195.736	18812.04
CTP	53833.12	47071.4	20867.84	8499.569	46512.43	121765.3	29472.48	19098.77	75987.16	28704.05	8605.31	107357.4	37456.5	79677.72	50839.61	8497.846	37973.94
UTP	116729.9	152095.1	104237.1	68849.9	125053.2	321888.4	98678.54	147360.5	221228.6	199362.1	61494.63	410905.9	100180.8	208925.9	150564.5	41107.14	131245.4
CDP-choline	52160.48	49629.9	35092.64	42529.62	45647.47	46902.72	59906.32	48561.19	55588.72	52007.56	47970.9	60848.07	50935.71	51731.59	29469.33	52124.18	39335.88
dATP	6281.455	7362.348	7770.387	4876.229	2310.072	5294.955	5001.086	3046.305	6678.939	7723.746	4790.115	6605.167	5747.362	6679.621	4997.899	4180.21	4009.355
Taurodeoxycholic acid	10789.99	8707.11	9016.194	7553.381	10500.32	6942.151	13573.34	8187.978	6943.639	9486.464	10553.68	11707.07	10548.85	10422.4	6282.973	8172.837	10824.22
ATP	1791762	890639	812195.2	482301.6	240754.3	1393700	1268069	2012398	427304.2	1831177	435186.2	2554800	1361944	573190.6	700858	714731.9	569907.2
GTP	44117.29	51720.06	46294.88	20966.96	19769.6	62558.02	61543.07	42960.25	39492.34	27926.69	32444.52	70734.76	79710.62	45511.42	38889.87	44879.03	62109.66
UDP-D-glucose	1709794	1785312	1397260	1594498	1473159	1540059	1998061	1594294	2154085	1621660	1637688	1809315	1628603	1829914	1325942	1630464	1494602
UDP-D-glucuronate	70629.1	81199.38	53444.47	52983.48	59738.78	83626.34	80028.23	78226.54	131780.7	81612.95	58140.6	102686.5	51841.15	65283.44	49068.06	53042.48	43585.03
ADP-D-glucose	47543.57	75209.93	30109.69	43006.71	49420.39	47727.17	46467.71	38611.3	139796.5	35520.47	52190.82	44236.81	32562.83	58113.31	33868.86	41384.12	31518.38
UDP-N-acetyl-glucosamine	2547166	2573947	2206598	2549251	2198732	2472965	3207541	2431092	2851736	2574812	2505282	2974703	2662892	2886125	2103151	2558650	2389105
glutathione disulfide	7429824	7665614	5212696	6882194	6667590	6895724	6788246	7024032	8616096	5897808	7630534	6950668	5732788	7453322	5604844	7359976	5112783
NADH	1599.887	1654.724	13151.04	2794.493	2308.918	1212.783	13838.63	838.6401	4296.135	12030.56	763.6149	7995	26587.84	1540.357	3869.646	1272.112	21055.41
NADP+	348657.2	345737.4	250254.5	330197.2	310579.8	326354.4	418116.9	307338.6	381088.3	321446.1	340980.4	357141.5	248507.8	317420.8	276939.1	322960.3	284189
NADPH	3138.851	1403.144	12909.52	4298.172	2355.393	4127.281	12120.96	1951.167	1136.761	12594.58	1171.482	18749.94	40525.05	3056.501	12041.28	5765.523	17184.72
coenzyme A	3347.414	2353.92	4780.933	4277.594	4553.836	2525.08	9121.794	1972.802	6390.637	9620.788	3308.227	8137.049	9185.495	5437.46	5434.268	3413.847	8956.352
FAD	150797.1	151211.2	106847.9	171419.6	122971.5	111272.1	219372	102270.7	134818.5	132911.8	170534.6	136304.2	162638.3	151742	116836.4	167159.1	174956
acetyl-CoA	5019.726	3432.652	5323.453	7888.635	2543.703	3332.806	4799.299	5005.633	9966.873	6053.379	8251.569	3316.802	5619.801	4375.07	13837.13	4924.275	7153.419
UDP	1861213	1044925	1654710	1996734	1049703	1367858	2212566	1732807	1429002	1937871	1860775	1698245	1950563	1559306	1692626	1922947	1697379
IMP	535946.2	1080314	272930.1	516113.5	1010777	777783.2	577929.2	424130.5	1802565	353277.7	526672.2	1002582	346018	691183.6	210808.5	450447.3	243930.9
GMP	2062837	1590076	1970777	2168259	1625935	1805807	2700235	1928668	1520557	2094453	1880006	2113082	1985683	1942694	1964303	2010358	2013188
xanthosine-5-phosphate	1981.383	3059.195	2236.756	2656.822	5251.479	3237.26	2705.877	1394.939	1906.945	2301.649	1616.905	4523.832	2578.433	2906.166	1851.521	1565.718	2151.573
Sedoheptoluse bisphosphate	49532.16	39341.52	41662.38	45045.29	35633.44	43953.85	52195.92	46886.82	38872.81	44721.19	43986.37	54510.09	41693.95	41261.82	47862.06	42660.49	44842.79
S-adenosyl-L-homoCysteine	346098.62	220918.31	285940.77	294111.21	237825.62	318385.83	452223.5	284257.36	257437.56	381531.05	317699.18	368984	358430.65	315743.88	227659.95	275025.58	301631.84
dCDP	275364.5	352613.6	181226.6	248842.7	352526.8	369367.9	396908.2	237795.6	263203.7	280377.2	231407.8	503623.3	266454	348617.1	176948.1	296949.5	205116.9
5-phosphoribosyl-1-pyrophosphate	3031.958	3381.33	3544.414	2669.581	3609.267	3700.835	2035.363	2562.436	4343.659	8754.762	2348.209	6147.215	2336.166	3494.143	4627.432	941.1808	2540.506
Octoluse Bisphosphate	21853.51	16820.65	22418.01	23480.88	17049.5	20418.13	25322.59	24838.46	18778.29	27200.43	24604.99	24084.64	21270.69	21488.21	26105.87	26755.77	20585.09
dTDP	361782.3	256014.2	276076.7	390125.9	230794.2	289597.8	471043.4	311464.8	329128.3	342238.9	328067	387514.8	354345.3	329585.6	290778.8	359974	316628
CDP	428348.2	254917.1	439842	449370.5	221115.9	298801.6	482825.8	434022.5	333991.6	522048.8	495694.1	378281.5	567157.4	388761.6	517584.1	506320.5	458313.8
D-gluconate	437580	463890.9	361512.1	448290.7	420454.25	398808.1	650498.2	373897.51	598921.2	471438.6	428014.3	624993	506120.4	523375.5	365958.57	485774.9	418918.4
Cholic acid	29468.586	25940.407	25859.301	25438.535	24748.67	22644.868	25808.99	23920.867	26646.135	27756.371	28459.119	29112.277	27835.577	26961.45	28039.411	29240.648	24512.459
adenosine 5'-phosphosulfate	5300.961	4367.645	5659.154	5827.33	1138.967	2831.234	7324.179	5770.41	8793.177	6149.241	6301.195	7749.458	5935.562	4152.518	3749.135	5336.797	5222.521
ADP	4511214	3356306	4460440	4779516	3021386	3367797	4799800	4344964	4443552	4368132	4336216	3831731	4244869	3847543	4469954	4463602	4301396
IDP	3309.936	7607.331	904.0745	2528.66	6080.72	3338.554	1186.936	3100.335	27151.42	922.5701	4240.98	1111.177	573.6037	4509.609	1269.359	2569.746	891.0364
folate	63062.76	63703.75	76871.65	69375.73	77233.35	60472.25	122455.9	55795.45	65035.26	103082.9	48367.78	96371.98	114418.8	67412.95	63097.95	55048.16	99181.8
GDP	433051.6	253837	397803.1	464262.8	260064.5	290201.8	406818.8	407104.9	331925.5	414208.7	431125.7	339115.3	490499.8	347975.3	553148.1	483220.2	419643.7
CDP-ethanolamine	2026130.2	1899176.1	1541563.9	1798435.8	1639906.4	1620282.1	2290355	1805233.1	1993563.8	1997754	1993536.7	2146934.3	2093397	2177515.6	1537832.6	2099070.8	1653003.2
Deoxycholic acid	18117.54	22939.67	25918.9	29523.12	29318.69	13606.17	18009.81	5388.724	2750.191	8822.618	3912.178	36116.44	5055.829	34715.84	19320.71	25913.42	22095.26
FMN	7011.922	6746.326	4809.912	6446.817	4300.384	3989.933	7732.907	6417.377	4950.842	7700.697	7354.835	6793.369	5395.004	5367.715	5675.067	6983.305	6139.5
cholesteryl sulfate	8120.625	7938.812	7108.877	7948.156	5599.324	7937.764	8062.121	6666.261	8630.949	8475.514	6464.229	7603.58	7256.859	7188.029	7535.584	8364.386	8158.359
dCTP	20395.04	18946.95	11961.94	2251.741	18832.23	7185.605	15450.87	1450.73	24833.14	8956.478	3234.182	4149.961	21402.88	8886.124	21005.07	1445.083	24851.26
nicotinate	6021.996	8253.573	4697.246	7042.362	10037.42	8733.766	10303.75	5332.651	8968.521	6439.158	5574.435	11614.41	7918.093	7744.763	4453.266	6359.207	4343.732
Pyroglutamic acid	595853.9	646964.18	590163.1	641511.6	674587.6	630759.74	676264.7	512313.81	1150090.6	599005.4	667023.1	817129	671019.5	727763.9	619970.5	821322.5	569284.7
Citraconic acid	54455.716	70631.797	37068.386	64556.59	50229.624	51080.122	68483.532	49536.066	137521.495	44625.587	61630.636	50804.692	48128.447	58463.355	49516.456	51527.044	39799.843
N-Acetyl-L-alanine	20300.67	22378.65	15566.96	26036.21	24343.78	21692.29	29725.99	18077.83	26599.47	18508.73	21644.54	29596.49	25119.58	29123.55	18816.53	24691.84	17951.87
Hydroxyisocaproic acid	10622.937	8921.087	8131.454	9130.793	10197.013	10605.506	8047.417	12863.134	9025.372	9625.878	11457.809	10290.188	8812.175	9122.843	8100.541	11929.423	8941.214
aspartate	444376	275616.3	345238.9	392010.8	224119.7	283617.4	591915.2	392251.7	328987.4	479004.3	449582.3	359528	464482.8	345964.4	340296.3	440565.8	412243.3
malate	157575.9	247770.8	162100.8	163537.5	223477.1	212871.5	214747	161007.9	252464	155872.4	167378.9	289885.7	185057.5	253508.2	144709.3	169457	173705.7
adenine	19501.37	14341.68	11734.32	12650.25	39877.82	18536.84	18258.33	15898.14	23871.12	28325.99	17242.86	16539.05	24388.57	24809.99	21828.62	10437.68	17954.92
a-ketoglutarate	163426.3	145701.6	121526.4	158358.2	148856.2	122477.8	208757.7	148788.9	144976	167417.3	152724.6	188045.6	179367.6	147926.6	104767.6	155750.3	135336.9
pyruvate	12382.34	13892.7	6163.285	13411.38	9335.771	5351.17	12830.82	6795.136	16550.83	8311.898	12497.71	7935.862	11829.77	8566.851	10939.1	9118.622	9620.124
lactate	165737.3	511932.3	93271.82	198019.3	320488.4	143971.6	93807.2	159056.8	1038075	75303.16	314990.3	154035.1	109005.5	276264.2	152742.7	187140.2	106672.2
acetoacetate	3268.7	2962.712	2156.782	3717.621	3084.417	3429.802	3095.184	3673.991	4578.154	3619.098	3263.607	3832.487	5166.231	3795.17	4752.161	5087.829	3215.327
dimethylglycine	1682165.8	1673874.8	1539589	1594749.3	1473916.7	1628659	1956414.3	1606622.9	1882458.8	1698922.1	1720155.3	1890817.8	1763959.6	1817611.5	1494124.2	1753420.6	1618311.2
4-aminobutyrate	846592.4	781304.7	756219.2	802189.8	710885.8	860585.8	1027812	802087.2	943302.7	894852	873199.5	960187.1	857984.2	867005.1	721752.8	878565.7	823727.8
glycerate	8694.807	11247.68	6796.381	10803.33	8943.817	6437.009	8859.032	9064.089	24593.04	6590.83	10201.92	9217.852	7266.437	11428.03	8585.241	9369.911	7231.777
fumarate	122100.298	191431.367	121840.206	138061.476	175535.827	173422.78	171524.338	134076.623	213356.18	120922.334	131187.662	231976.01	144133.427	188755.857	109362.761	139790.174	135664.525
succinate	113947	118686.5	90289	124933.9	106147.1	105618.2	147843.2	116071.1	123886.2	119806.8	107988.8	133324.6	122616.5	130205	87881.15	109866.5	96001.1
purine	4721.577	3733.48	2679.688	3585.038	2657.857	4903.525	4949.534	5149.379	9617.103	3309.502	4595.417	3701.716	3237.369	4695.717	4071.152	5001.277	3138.961
myo-inositol	7282.278	12281.161	3085.82	6010.987	6720.047	4573.219	5460.53	6537.11	27394.607	3214.117	8699.017	5770.23	6445.271	8505.686	5166.593	6322.366	3760.658
dihydroxy-acetone-phosphate	784.1943	2234.088	564.7554	722.4645	721.6626	740.8591	480.2976	490.4869	7663.577	595.6085	1503.326	768.4969	334.0028	1224.774	707.3986	1327.861	657.1722
sn-glycerol-3-phosphate	202138.376	338475.29	163800.098	203520.647	283172.091	308360.481	228666.455	178307.647	481174.981	173652.6395	212335.607	419685.993	182237.06	345859.709	231377.222	196199.345	180680.674
aconitate	3970.919	5907.606	5208.619	5367.786	3974.196	5939.849	6287.196	5836.469	5443.857	6206.502	6861.113	6449.994	5900.737	6065.137	6861.518	7454.352	6596.251
N-carbamoyl-L-aspartate	8091.228	5113.994	10031.65	229622.1	117661.4	94790.38	197560.2	3015.65	10261.56	8651.965	3389.031	151750.3	8211.169	4566.638	10872.42	2431.637	11755.51
glucono-δ-lactone	21429.585	56764.27	6208.455	20514.751	30966.91	22166.943	10751.792	19684.604	157032.679	7341.9688	36234.373	9742.974	9521.641	30290.107	8008.587	20704.895	7440.927
hydroxyphenylpyruvate	5118.092	4737.145	7239.87	7009.206	5758.816	7415.625	7707.557	4006.679	6505.334	4390.304	7084.9	7618.775	4017.286	7402.711	7119.011	6511.788	6767.952
4-Pyridoxic acid	3419.491	3091.039	2950.101	2847.941	1703.807	2764.933	4187.595	3152.817	3266.269	3755.956	3223.087	5263.261	3066.29	3535.59	1976.094	2993.477	2754.834
3-phospho-serine	50324.56	55851.95	37401.72	48900.83	42782.72	43224.14	66626.66	52483.14	59221.02	57668.08	53440.34	58057.74	61297.57	53359.1	44520.18	64797.5	42748.08
3-phosphoglycerate	43239.43	82625.8	26447.64	48917.79	45388	45836.88	32869.86	49438.14	280506.4	25297.62	80416.12	35899.52	27899.24	54579.28	42059.83	49942.66	28311.09
N-acetyl-glutamate	174597.35	138707.07	138954.83	148447.59	143105.56	141788.45	198507.72	147257	42175.76	157822.26	158822.03	198585.7	49127.9846	192728.05	139231.25	161454.23	141533.16
isocitrate	111538.279	122790.527	120384.851	118981.603	94655.334	111614.996	159282.961	113612.332	107063.974	132948.96	129632.528	112607.795	130287.395	131624.677	141478.537	137553.112	118829.989
citrate/isocitrate	111538.279	122790.527	120384.851	118981.603	94655.334	111614.996	159282.961	113612.332	107063.974	132948.96	129632.528	112607.795	130287.395	131624.677	141478.537	137553.112	118829.989
citrate	111538.279	122790.527	120384.851	118981.603	94655.334	111614.996	159282.961	113612.332	107063.974	132948.96	129632.528	112607.795	130287.395	131624.677	141478.537	137553.112	118829.989
glutamate	3619321	3594990	3258800	3384558	3274031	3451142	4115102	3477887	3990080	3523724	3697474	4097475	3807653	4210071	3202427	3819671	3494475
3-methylphenylacetic acid	1929.503	919.2664	1193.969	1125.41	7777.826	1505.324	1121.131	5316.571	5163.824	2392.48	1785.234	713.0798	2921.282	4114.876	935.3358	1495.674	1246.113
orotate	956.284	23378.25	1033.199	28949.19	32202.44	22714.33	34071.86	976.9192	1339.526	1231.057	1294.24	42427.64	2212.28	1275.749	1693.352	1237.618	742.0859
dihydroorotate	1027.633	1297.913	1233.347	69084.39	29660.68	17039.18	47750.46	306.1908	1145.342	594.1436	375.1951	36804.09	1184.816	791.6589	1156.09	229.3602	879.7903
2-Aminooctanoic acid	265045	365441.2	357575.5	546384.3	536420.5	240128.2	299346.3	267797.2	173957.1	188842.5	147921.2	478866.5	169441.2	499800.3	545842.3	532180.6	357685.2
Indole-3-carboxylic acid	139.2836	6381.281	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
phenylalanine	17668.31	21486.58	14360.29	22382.84	21575.56	19667.52	22132.38	18079.8	41613.88	16687.47	32171.86	25961.24	15907.88	25110.84	16746.31	18101.36	12387.23
Phenyllactic acid	14600.2	15057.62	24338.12	20688.08	19837.47	22756.17	21667.51	12440.24	22196.76	13730.58	25900.53	21672.97	12641.1	19906.1	21442.08	17076.78	17754.12
Atrolactic acid	14600.2	15057.62	24338.12	20688.08	19837.47	22756.17	21667.51	12440.24	22196.76	13730.58	25900.53	21672.97	12641.1	19906.1	21442.08	17076.78	17754.12
phosphoenolpyruvate	31021.585	26724.558	21804.114	26337.834	25054.9552	34026.89	33635.686	51349.068	53762.561	36268.177	26373.3106	44934.79	21970.719	27122.019	24104.747	25289.0184	22795.334
Uric acid	0	2812.283	1340.989	4644.339	2064.1	900.1575	0	178.4658	3014.209	1626.756	316.4884	1549.336	5743.206	795.8619	2938.68	2971.579	726.3682
Pyridoxamine	6182.623	4293.046	7836.536	6668.022	5980.613	4955.098	8817.437	5369.21	8246.931	6273.576	4102.688	8758.28	8329.211	6577.184	6631.494	5644.844	6753.435
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
guanosine
dCMP
N-acetyl-glucosamine-1/6-phosphate
7-methylguanosine
S-methyl-5'-thioadenosine
D-sedoheptulose-1/7-phosphate
glutathione
6-phospho-D-gluconate
inosine
1_3-diphopshateglycerate
2_3-Diphosphoglyceric acid
dTMP
CMP
UMP
cyclic-AMP
dAMP
aminoimidazole carboxamide ribonucleotide
fructose-1-6-bisphosphate
dGMP
D-erythrose-4-phosphate
NG-dimethyl-L-arginine
tryptophan
pantothenate
AMP
thymidine
glucose-6-phosphate
glucose-1-phosphate
dTTP
CTP
UTP
CDP-choline
dATP
Taurodeoxycholic acid
ATP
GTP
UDP-D-glucose
UDP-D-glucuronate
ADP-D-glucose
UDP-N-acetyl-glucosamine
glutathione disulfide
NADH
NADP+
NADPH
coenzyme A
FAD
acetyl-CoA
UDP
IMP
GMP
xanthosine-5-phosphate
Sedoheptoluse bisphosphate
S-adenosyl-L-homoCysteine
dCDP
5-phosphoribosyl-1-pyrophosphate
Octoluse Bisphosphate
dTDP
CDP
D-gluconate
Cholic acid
adenosine 5'-phosphosulfate
ADP
IDP
folate
GDP
CDP-ethanolamine
Deoxycholic acid
FMN
cholesteryl sulfate
dCTP
nicotinate
Pyroglutamic acid
Citraconic acid
N-Acetyl-L-alanine
Hydroxyisocaproic acid
aspartate
malate
adenine
a-ketoglutarate
pyruvate
lactate
acetoacetate
dimethylglycine
4-aminobutyrate
glycerate
fumarate
succinate
purine
myo-inositol
dihydroxy-acetone-phosphate
sn-glycerol-3-phosphate
aconitate
N-carbamoyl-L-aspartate
glucono-δ-lactone
hydroxyphenylpyruvate
4-Pyridoxic acid
3-phospho-serine
3-phosphoglycerate
N-acetyl-glutamate
isocitrate
citrate/isocitrate
citrate
glutamate
3-methylphenylacetic acid
orotate
dihydroorotate
2-Aminooctanoic acid
Indole-3-carboxylic acid
phenylalanine
Phenyllactic acid
Atrolactic acid
phosphoenolpyruvate
Uric acid
Pyridoxamine
METABOLITES_END
#END